A heat shock protein based polyvalent vaccine targeting HSV-2: CD4(+) and CD8(+) cellular immunity and protective efficacy.
Vaccine
; 29(47): 8530-41, 2011 Nov 03.
Article
en En
| MEDLINE
| ID: mdl-21767588
ABSTRACT
Efforts to develop a subunit vaccine against genital herpes have been hampered by lack of knowledge of the protective antigens of HSV-2, the causative agent of the disease. Vaccines based either on selected antigens or attenuated live virus approaches have not demonstrated meaningful clinical activity. We present here results of a therapeutic vaccine candidate, HerpV (formerly called AG-707), consisting of 32 HSV-2 peptides derived from 22 HSV-2 proteins, complexed non-covalently to the HSP70 chaperone and formulated with QS-21 saponin adjuvant. HerpV is observed to be immunogenic, generating CD4(+) and CD8(+) T cell responses in three mouse strains including HLA-A2 transgenic mice. Optimal T cell stimulation was dependent on the synergistic adjuvant properties of QS-21 with hsp70. The vaccine provided significant protection from viral challenge in a mouse prophylaxis model and showed signals of activity in a guinea pig therapeutic model of existing infection. Peripheral blood mononuclear cells from human HSV-2(+) subjects also showed reactivity in vitro to a subset of individual peptides and to the pool of all 32 peptides. Recombinant human Hsc70 complexed with the 32 peptides also stimulated the expansion of CD8(+) T cells from HSV-2(+) subjects in vitro. These studies demonstrate that HerpV is a promising immunotherapy candidate for genital herpes, and provide a foundation for evaluating HerpV in human HSV-2(+) subjects with the intent of eliciting CD4(+) and CD8(+) T cell responses to a broad array of viral antigens.
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Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales
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Linfocitos T CD4-Positivos
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Herpesvirus Humano 2
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Linfocitos T CD8-positivos
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Vacunas contra el Virus del Herpes Simple
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Proteínas del Choque Térmico HSC70
Idioma:
En
Revista:
Vaccine
Año:
2011
Tipo del documento:
Article